Kotsiou Ourania S, Kirgou Paraskevi, Siachpazidou Dimitra, Bartziokas Konstantinos, Tourlakopoulos Konstantinos, Malli Foteini, Pinaka Maria, Daniil Zoe, Gourgoulianis Konstantinos I
Laboratory of Human Pathophysiology, Department of Nursing, University of Thessaly, Gaiopolis, Larissa, Greece.
Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, Larissa, Greece.
ERJ Open Res. 2025 Jun 23;11(3). doi: 10.1183/23120541.00939-2024. eCollection 2025 May.
Severe eosinophilic asthma adversely affects small airway function, but effective therapeutic options are limited. The IMPOSE trial (www.clinicaltrials.gov identifier number NCT05147155) assessed the early and sustained effects of mepolizumab on small airways in patients with severe eosinophilic asthma using impulse oscillometry (IOS).
The study comprised 130 participants: 40 with uncontrolled severe asthma initiating mepolizumab, 40 with well-controlled severe asthma and 50 healthy controls. Lung function was assessed with IOS, spirometry and plethysmography at baseline and at 1, 3 and 6 months post-treatment. Clinical outcomes included asthma control, quality of life and medication adherence.
Small airway function significantly improved within 1 month of mepolizumab initiation, shown by reductions in resonance frequency ( ), indicating decreased small airway resistance undetectable by spirometry. By 6 months, sustained improvements in forced expiratory flow at 25-75% of forced vital capacity, total lung capacity % of predicted value, , area under the reactance curve and the difference in resistance between 5 and 20 Hz ( ) were evident, accompanied by better asthma control and quality-of-life scores. Negative correlations between change in resistance at 5 Hz and change in with change in Asthma Control Test score at 6 months suggested that decreased small-airway resistance and heterogeneity correlated with improved asthma control. These benefits were particularly prominent in patients without fixed airway obstruction. Notably, even patients with irreversible airflow limitations saw improvements in small airway dysfunction, suggesting that mepolizumab may provide benefits even in cases of irreversible airway changes.
This study is the first to demonstrate that mepolizumab has a rapid and sustained therapeutic effect on small airways in severe eosinophilic asthma, as shown by IOS. IOS proves to be a valuable tool for monitoring the effects of biologic treatments on small airway function, revealing insights beyond those provided by spirometry.
重度嗜酸性粒细胞性哮喘对小气道功能有不利影响，但有效的治疗选择有限。IMPOSE试验（www.clinicaltrials.gov标识符编号NCT05147155）使用脉冲振荡法（IOS）评估了美泊利珠单抗对重度嗜酸性粒细胞性哮喘患者小气道的早期和持续影响。
该研究包括130名参与者：40名未控制的重度哮喘患者开始使用美泊利珠单抗，40名控制良好的重度哮喘患者和50名健康对照者。在基线以及治疗后1、3和6个月时，使用IOS、肺量计和体积描记法评估肺功能。临床结局包括哮喘控制、生活质量和药物依从性。
在开始使用美泊利珠单抗的1个月内，小气道功能显著改善，表现为共振频率降低（），这表明小气道阻力降低，而肺量计无法检测到这种变化。到6个月时，用力肺活量25%-75%时的用力呼气流量、肺总量占预测值的百分比、（）、电抗曲线下面积以及5至20赫兹之间的阻力差（）持续改善，同时哮喘控制和生活质量评分也有所提高。5赫兹时阻力变化与（）变化之间的负相关性以及6个月时哮喘控制测试评分的变化表明，小气道阻力降低和异质性与哮喘控制改善相关。这些益处在无固定气道阻塞的患者中尤为显著。值得注意的是，即使是有不可逆气流受限的患者，其小气道功能障碍也有所改善，这表明美泊利珠单抗即使在气道发生不可逆变化的情况下也可能带来益处。
本研究首次证明，如IOS所示，美泊利珠单抗对重度嗜酸性粒细胞性哮喘的小气道具有快速且持续的治疗效果。IOS被证明是监测生物治疗对小气道功能影响的有价值工具，可以揭示肺量计无法提供的见解。
